한빛사 논문
Hong-pyo Lee1, Farid Alisafaei2, Kolade Adebawale3, Julie Chang4, Vivek B. Shenoy2 and Ovijit Chaudhuri1,*
1Department of Mechanical Engineering, Stanford University, Stanford, CA, USA.
2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
3Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
4Department of Bioengineering, Stanford University, Stanford, CA, USA.
*Corresponding author.
Abstract
Cell migration in confining microenvironments is limited by the ability of the stiff nucleus to deform through pores when migration paths are preexisting and elastic, but how cells generate these paths remains unclear. Here, we reveal a mechanism by which the nucleus mechanically generates migration paths for mesenchymal stem cells (MSCs) in confining microenvironments. MSCs migrate robustly in nanoporous, confining hydrogels that are viscoelastic and plastic but not in hydrogels that are more elastic. To migrate, MSCs first extend thin protrusions that widen over time because of a nuclear piston, thus opening up a migration path in a confining matrix. Theoretical modeling and experiments indicate that the nucleus pushing into the protrusion activates mechanosensitive ion channels, leading to an influx of ions that increases osmotic pressure, which outcompetes hydrostatic pressure to drive protrusion expansion. Thus, instead of limiting migration, the nucleus powers migration by generating migration paths.
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